Consumer behavior throughout the world points to a high level of dissatisfaction with currently available contraceptive methods. Almost a third of American women discontinue using hormonal methods of birth control within the first year, while ~54% of men discontinue using condoms within the same timeline. Consumers are not satisfied with either the continual methods (hormonal) or the on-demand option (such as condoms). It is well documented that conventional steroid-based hormonal contraceptives are associated with powerful side effects, because of their pleiotropic mode of action on various cell types. Hormones cross cellular membranes and are entrapped inside the cells, where they alter gene expression and can have prolonged effects on a variety of physiological mechanisms, including neuronal functions. Therefore, despite being highly effective, the numerous undesirable side effects associated with hormonal contraceptives often lead to discontinuation by women and leaves a huge segment of the consumer market underserved. In exploring new non-hormonal methods targeting sperm functions, contraceptives can either target spermatogenesis or impair the later stages of sperm activation, a preferable target. Mature sperm cells have a distinct set of specific molecular targets, which increases the possibility to develop a non-hormonal contraceptive drug with high specificity and low side effects. Such a compound will prevent fertilization, by disabling the sperm cells once they have entered the women's reproductive tract, and could be developed as an on-demand, non- hormonal contraceptive. This project will comprehensively evaluate the family of small molecules known as triterpenes for the development of on-demand non-hormonal female contraceptives. In earlier published work, some of these compounds were shown to target sperm activation pathways that are vital for fertility. Our company YourChoice Therapeutics proposes to use in vitro assays to evaluate compounds that will inhibit sperm motility and activation. Once we identify the lead compound, we will embed the drug into an innovative delivery system, to develop a non- hormonal on-demand contraceptive that will be easy to deliver. This innovative technology will provide an alternative to the current global hormonal contraceptive market providing a new family planning method to over 1.6 billion women of reproductive age worldwide.